Study Of Sunitinib Malate Versus Sorafenib In Patients With Inoperable Liver Cancer

• ClinicalTrials.gov Identifier: NCT00699374
• Recruitment Status: Terminated
• First Posted: June 18, 2008
• Results First Posted: January 14, 2013
• Last Update Posted: January 14, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 16, 2008
• First Posted Date: June 18, 2008
• Results First Submitted Date: December 7, 2012
• Results First Posted Date: January 14, 2013
• Last Update Posted Date: January 14, 2013
• Study Start Date: July 2008
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2012)

Overall Survival (OS) [ Time Frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150 ]

Overall survival is the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

• Original Primary Outcome Measures (submitted: June 16, 2008): Overall Survival [ Time Frame: From screening/baseline to patient death ]

Current Secondary Outcome Measures (submitted: December 7, 2012)

• Progression-Free Survival (PFS) [ Time Frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150 ]
  The period from randomization until disease progression or death.
• Time to Tumor Progression (TTP) [ Time Frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150 ]
  Time in weeks from randomization to first documentation of objective tumor progression or death due to cancer, whichever comes first. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD])
• European Quality of Life (EQ-5D)- Health State Profile Utility Score [ Time Frame: Day 1 of each cycle ]
  EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula assigns a utility value for each domain in the profile. Score is transformed and results in a score range -0.594 to 1.000; higher score indicates better health state.

Original Secondary Outcome Measures (submitted: June 16, 2008)

• Progression Free Survival [ Time Frame: From Screening/baseline until patient progression or death ]
• Time to Tumor Progression [ Time Frame: From screening/baseline until patient progression ]
• Safety (adverse events and laboratory abnormalities) [ Time Frame: From screening/baseline to end of study treatment ]
• Health Status [ Time Frame: From baseline to end of study treatment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Of Sunitinib Malate Versus Sorafenib In Patients With Inoperable Liver Cancer
• Official Title: A Multinational, Randomized, Open-Label, Phase 3 Study Of Sunitinib Malate Versus Sorafenib In Patients With Advanced Hepatocellular Carcinoma
• Brief Summary: The study will evaluate the efficacy and safety of sunitinib (Arm A), given at 37.5 mg orally once daily, compared to sorafenib (Arm B), given orally at 400 mg twice daily, in patients with inoperable liver cancer. A total number of 1200 patients will be enrolled, 600 on Arm A and 600 on Arm B. Study treatment may be adjusted based on patient tolerance. and will be given until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of study treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival.
• Detailed Description: This study was terminated on April 22th, 2010, based on a higher incidence of serious adverse events in the sunitinib arm compared to the sorafenib arm, and the fact that sunitinib did not meet the criteria to demonstrate that it was either superior or non-inferior to sorafenib in the survival of patients with advanced hepatocellular cancer. Patients on sunitinib who are judged by the investigator as receiving clinical benefit may chose to remain on study and continue treatment with sunitinib until clinical benefit as per the investigator's judgment.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Hepatocellular

Intervention

• Drug: sunitinib malate
  sunitinib capsules at starting dose of 37.5 mg PO daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sunitinib dosing interruptions and/or reductions are allowed based on patient tolerability.
  Other Name: Sutent®
• Drug: sorafenib
  sorafenib tablets at starting dose of 400 mg PO twice daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sorafenib dosing interruptions and/or reductions are allowed based on patient tolerability.
  Other Name: Nexavar®

Study Arms

• Experimental: Arm A
  sunitinib arm
  Intervention: Drug: sunitinib malate
• Active Comparator: Arm B
  sorafenib arm
  Intervention: Drug: sorafenib

Publications *

• Abuhelwa AY, Badaoui S, Yuen HY, McKinnon RA, Ruanglertboon W, Shankaran K, Tuteja A, Sorich MJ, Hopkins AM. A clinical scoring tool validated with machine learning for predicting severe hand-foot syndrome from sorafenib in hepatocellular carcinoma. Cancer Chemother Pharmacol. 2022 Apr;89(4):479-485. doi: 10.1007/s00280-022-04411-9. Epub 2022 Feb 28.
• Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013 Nov 10;31(32):4067-75. doi: 10.1200/JCO.2012.45.8372. Epub 2013 Sep 30.
• Koeberle D, Montemurro M, Samaras P, Majno P, Simcock M, Limacher A, Lerch S, Kovacs K, Inauen R, Hess V, Saletti P, Borner M, Roth A, Bodoky G. Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06). Oncologist. 2010;15(3):285-92. doi: 10.1634/theoncologist.2009-0316. Epub 2010 Mar 4.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 26, 2012): 1075
• Original Estimated Enrollment (submitted: June 16, 2008): 1200
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically-confirmed diagnosis of hepatocellular carcinoma
• presence of measurable disease by radiographic imaging
• Child-Pugh class A
• ECOG PS 0 or 1
• adequate organ function.

Exclusion Criteria:

• Prior treatment with any systemic treatment for hepatocellular carcinoma
• prior local treatment within 4 weeks from entry
• presence of clinically relevant ascites
• severe hemorrhage <4 weeks of starting study treatment
• known HIV or serious acute or chronic illness
• current treatment on another clinical trial
• pregnancy or breastfeeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Malaysia, Philippines, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00699374
• Other Study ID Numbers: A6181170
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: December 2012